Current Reviews in Clinical and Experimental Pharmacology最新文献

Background: Many medications have different pharmacokinetics in children than in adults. Knowledge about the safety and efficacy of medications in children requires research into the pharmacokinetic profiles of children's medicines. By analysing registered clinical trial records, this study determined how frequently pharmacokinetic data is gathered in paediatric drug trials.

Methods: We searched for the pharmacokinetic data from clinical trial records for preterm infants and children up to the age of 16 from January 2011 to April 2022. The records of trials involving one or more drugs in preterm infants and children up to the age of 16 were examined for evidence that pharmacokinetic data would be collected.

Results: In a total of 1483 records of interventional clinical trials, 136 (9.17%) pharmacokinetic data involved adults. Of those 136 records, 60 (44.1%) records were pharmacokinetics trials involving one or more medicines in children up to the age of 16.20 (33.3%) in America, followed by 19 (31.6%) in Europe. Most trials researched medicines in the field of infection or parasitic diseases 20 (33.3%). 27 (48.2%) and 26 (46.4%) trials investigated medicines that were indicated as essential medicine.

Conclusion: The pharmacokinetic characteristics of children's drugs need to be better understood. The current state of pharmacokinetic research appears to address the knowledge gap in this area adequately. Despite slow progress, paediatric clinical trials have experienced a renaissance as the significance of paediatric trials has gained international attention. The outcome of paediatric trials will have an impact on children's health in the future. In recent years, the need for greater availability and access to safe child-size pharmaceuticals has received a lot of attention.

Background: P2Y₁₂ inhibitors have been widely used as an alternative to aspirin in clinical practice for secondary stroke prevention. We aimed to compare the efficiency and safety of P2Y₁₂ inhibitors and aspirin for stroke prevention in patients with previous stroke or transient ischaemic attack (TIA).

Methods: PubMed, Embase, and Cochrane Central Register of Controlled Trials were searched. All randomized trials that compared P2Y₁₂ inhibitors with aspirin among patients with stroke were included. The primary efficacy outcomes of our meta-analysis included stroke, vascular events, and all-cause death. The primary safety outcome was minor or major bleeding events.

Results: The search identified 4 randomized clinical trials comparing P2Y₁₂ inhibitors with aspirin for secondary stroke prevention that collectively enrolled 24508 patients (12253 received P2Y₁₂ inhibitor and 12255 received aspirin). Pooled results from the random-effects model showed that there were no significant differences in the risk of any stroke (OR 0.90 (0.78-1.04); I²=56.9%), vascular event (OR 0.91 (0.74-1.13); I²=78.3%), all-cause death (OR 0.98 (0.83-1.17); I²=0%), or minor or major bleeding (OR 1.13 (0.70-1.82); I²=79%) among patients who received a P2Y₁₂ inhibitor or aspirin. P2Y₁₂ inhibitors were associated with a significantly lower risk of recurrent ischaemic stroke (OR 0.84 (0.73- 0.96); I²=25%) than aspirin.

Conclusion: This meta-analysis suggests that P2Y₁₂ inhibitors are more effective than aspirin in preventing recurrent ischaemic stroke among ischaemic stroke patients despite the absence of any effect on a new ischaemic or haemorrhagic stroke, a new clinical vascular event, all-cause death, and major or minor bleeding events.

Background: We assessed the extent to which urinary and fecal excretion of 14C-labeled drug material in animal ADME studies was predictive of human ADME studies. We compared observed plasma elimination half-lives for total drug-related radioactivity in humans to pre-study predictions, and we estimated the impact of any major differences on human dosimetry calculations.

Methods: We included 34 human ADME studies with doses of 14C above 0.1 MBq. We calculated ratios of dosimetry input parameters (percentage fecal excretion in humans versus animals; observed half-life in humans versus predicted pre-study) and output parameters (effective dose post-study versus pre-study) and assessed their relationship.

Results: A quantitative correlation assessment did not show a statistically significant correlation between the ratios of percentages of 14C excreted in feces and the ratios of dosimetry outcomes in the entire dataset, but a statistically significant correlation was found when assessing the studies that were based on ICRP 60/62 (n=19 studies; P=0.0028). There also appeared to be a correlation between the plasma half-life ratios and the ratios of dosimetry results. A quantitative correlation assessment showed that there was a statistically significant correlation between these ratios (P<0.0001).

Conclusion: In all cases where the plasma elimination half-life for 14C in humans was found to be longer than the predicted value, the radiation burden was still within ICRP Category IIa. Containment of the actual radiation burden below the limit of 1.00 mSv appeared to be determined partly also by our choice to limit 14C doses to 3.7 MBq.

Background: Opioid analgesics used to treat pain can cause respiratory depression. However, this effect has not been extensively studied, and life-threatening, opioid-induced respiratory depression remains difficult to predict. We tested the ventilatory response to hypercapnia for evaluating the pharmacodynamic effect of a drug on respiratory depression.

Methods: We conducted a randomized, placebo-controlled, double-blind, crossover study on 12 healthy adult males. Subjects received 2 treatments (placebo and immediate-release oxycodone 30 mg) separated by a 24-hour washout period. Subjects inhaled a mixture of 7% carbon dioxide, 21% oxygen, and 72% nitrogen for 5 minutes to assess respiratory depression. Minute ventilation, respiratory rate, tidal volume, flow rate, end-tidal CO2, and oxygen saturation were recorded continuously at pre-dose and 30, 60, 120, and 180 minutes post-dose. The primary endpoint was the effect on the ventilatory response to hypercapnia at 60 minutes post-dose, as assessed by the slope of the linear relationship between minute ventilation and end-tidal CO2.

Results: At 60 minutes post-dose, subjects had a mean slope of 2.4 in the oxycodone crossover period, compared to 0.1 in the placebo period (mean difference, 2.3; 95% CI: 0.2 to 4.5; p = 0.035). Statistical significance was likewise achieved at the secondary time points (30, 120, and 180 minutes post-dose, p <0.05).

Conclusions: This model for testing ventilatory response to hypercapnia discriminated the effect of 30 mg of oxycodone vs. placebo for up to 3 hours after a single dose. It may serve as a method to predict the relative effect of a drug on respiratory depression.

Background: Patent Ductus Arteriosus (PDA) is associated with adverse clinical outcomes in very low birth weight (<1500g) infants.

Objective: In our study, it was aimed to investigate the effect of gentamicin treatment, which is frequently used for early-onset sepsis on ductal patency.

Methods: We performed a single-center retrospective review of charts of preterm infants <32 weeks gestation with birth weight <1500 grams born between June 1, 2015 and December 31, 2019 at the neonatal intensive care unit. All infants underwent an echocardiogram (ECHO) at 72 hours. To determine the effect of gentamicin treatment on hemodynamically significant PDA (hsPDA), we compared the frequency and duration of gentamicin administration between infants with hsPDA and without hsPDA.

Results: During the study period, 792 patients were evaluated. Gentamicin was given to more infants with hsPDA than to those without hsPDA (89.2% vs. 64.6%, p<0.001), and the duration of therapy was longer in those infants with hsPDA (7 days vs. 9 days, p<0.001). The area under the curve for duration of gentamicin was 0.772 (%95 CI: 0.742-0.804, P=0.0001), sensitivity: 59 (%95 CI: 53-65), specificity: 82 (%95 CI: 78-88), with a cut-off day for duration of gentamicin >7 days.

Conclusion: In our study, it was found that ductal contraction decreased and hsPDA rate increased as the rate and duration of gentamicin increased.

Background: Several studies reported that abnormal behavior was noted in pediatric patients receiving several drugs, including neuraminidase inhibitors (NIs). However, the information on drugs associated with abnormal behavior in a real-world setting remains limited. The purpose of this study was to clarify the drugs associated with abnormal behavior using a spontaneous reporting system database.

Methods: We performed a retrospective pharmacovigilance disproportionality analysis using the Japanese Adverse Drug Event Report database. Adverse event reports submitted to the Pharmaceuticals and Medical Devices Agency were analyzed, and the reporting odds ratio at 95% confidence interval were calculated.

Results: A total of 1,144 reports of abnormal behavior were identified. The signals were detected through the association of 4 neuraminidase inhibitors (oseltamivir, zanamivir, laninamivir, and peramivir) with the abnormal behaviour. These signals were stronger for oseltamivir than other neuraminidase inhibitors. The signals were also detected for acetaminophen and montelukast.

Conclusion: Our results should be able to raise physicians' awareness of drugs associated with abnormal behavior, but further investigation of these medications is warranted.